Pharmacokinetics and biodistribution of near-infrared fluorescence polymeric nanoparticles.

There has been increased interest in the use of polymeric nanoparticles as carriers for near-infrared fluorescence (NIRF) dyes for cancer diagnosis. However, efficient delivery of nanoparticles to the tumors after systemic administration is limited by various biobarriers. In this study, we investigated the pharmacokinetics, biodistribution, and tumor uptake of sub-nanometer sized polymeric nanoparticles (<100 nm in diameter) coated with polyethylene glycol in tumor-bearing mice. To facilitate our studies, these particles were labeled with gamma emitter indium-111. We found that two NIRF nanoparticles having the same size (approximately 20 nm) and chemical composition but different structures (i.e., hydrogel versus core-shell nanolatex), or the same core-shell nanolatex particles with different sizes (20, 30, and 60 nm), had different blood circulation times, biodistribution, and tumor uptake. Interestingly, the tumor uptake of the nanolatex particles correlated well with their blood residence times (R(2) = 0.95), but similar correlations were not found between nanogel and nanolatex particles (R(2) = 0.05). These results suggest that both the blood circulation time and the extent of hydration of the nanoparticles play an important role in the tumor uptake of nanoparticles. Prolonged blood circulation of these NIRF nanoparticles allowed clear visualization of tumors with gamma-scintigraphy and optical imaging after intravenous administration. A better understanding with regard to how the characteristics of nanoparticles influence their in vivo behavior is an important step towards designing NIRF nanoparticles suitable for molecular imaging applications and for efficient tumor delivery.

Study on the inhibitory effect of furafylline and troleandomycin in the 7-methoxyresorufin-O-demethylase and nifedipine oxidase activities in hepatic microsomes from four poultry species using high-performance liquid chromatography coupled with fluorescence and ultraviolet detection.

The present study reports the in vitro studies with furafylline and troleandomycin (TAO) as specific inhibitors of activities 7-methoxyresorufin-O-demethylase (MROD) and nifedipine oxidase, catalyzed by cytochrome P450 1 A2 (CYP1 A2) and 3A4 human enzymes, respectively, in hepatic microsomes of quail, duck, turkey and chicken. The results suggest that in chicken and quail the MROD activity is carried out by orthologs CYP1 A4 and 1 A5, meanwhile in duck and turkey by a CYP1 A5 ortholog. The nifedipine oxidase activity is carried out by orthologs of the CYP3A family in the four bird species. The use of furafylline and TAO significantly decreased these activities (P < 0.05) and suggested that the biotransformation of resorufin methyl ether (RME) may be related to more than one avian ortholog.

Characterizing property distributions of polymeric nanogels by size-exclusion chromatography.

Nanogels are highly branched, swellable polymer structures with average diameters between 1 and 100nm. Size-exclusion chromatography (SEC) fractionates materials in this size range, and it is commonly used to measure nanogel molar mass distributions. For many nanogel applications, it may be more important to calculate the particle size distribution from the SEC data than it is to calculate the molar mass distribution. Other useful nanogel property distributions include particle shape, area, and volume, as well as polymer volume fraction per particle. All can be obtained from multi-detector SEC data with proper calibration and data analysis methods. This work develops the basic equations for calculating several of these differential and cumulative property distributions and applies them to SEC data from the analysis of polymeric nanogels. The methods are analogous to those used to calculate the more familiar SEC molar mass distributions. Calibration methods and characteristics of the distributions are discussed, and the effects of detector noise and mismatched concentration and molar mass sensitive detector signals are examined.

Significant reduction of ATP production in PHA-activated CD4+ cells in 1-day-old blood from transplant patients.

BACKGROUND: Global immunosuppression can be measured by assessing adenosine triphospate (ATP) levels in mitogen-stimulated CD4+ T cells. METHODS: We investigated the effect of storage time on ATP levels in 234 blood samples from 18 healthy individuals and 152 transplant patients. The difference between day 0 (<13 hours post-blood draw) and day 1 (24-37 hours) measurements was analyzed and compared with various factors; a subset of samples was also analyzed in 6-hour intervals. RESULTS: The ATP levels were significantly lower on day 1 compared with that on day 0 in healthy individuals (279±159 vs 414±159 ng/mL, P<0.001) and patients (356±209 vs 455±221 ng/mL, P<0.0001). Of the 18 healthy individuals, 17 showed ATP reduction, whereas 192 (89%) of 216 patients did so on day 1 (24.8±24.1%). In the time course analysis, ATP levels decreased with the blood storage time in healthy and patient samples, and the reduction began as early as 7 hours post-blood draw. The reduction rate was significantly higher in patient samples with low day 0 ATP levels compared with samples with moderate or high levels (44.7±31.3% vs 23.2±23.6% or 18.7±15.7%; P<0.001). The reduction rate in patients treated with alemtuzumab induction was slightly higher than that in daclizumab-treated patients (28.8±24.6% vs 21.3±21.3%, P=0.09). CD4+ cell number did not change within 24 hours post-blood draw, but CD4 expression decreased 2.0±2.8% (P<0.05). CONCLUSIONS: The ATP levels are significantly lower in 1-day-old blood compared with fresh blood, suggesting that fresh blood should be used for assessing the T cell immune function to obtain the most accurate results.